title: Mesenchymal stem cells restore lung function by recruiting resident and nonresident proteins.
abstract: Because human lungs are unlikely to repair or regenerate beyond the cellular level, cell therapy has not previously been considered for chronic irreversible obstructive lung diseases. To explore whether cell therapy can restore lung function, we administered allogenic intratracheal  mesenchymal stem cells (MSCs) in the trachea of rats with chronic thromboembolic pulmonary hypertension (CTEPH), a disease characterized by single or recurrent pulmonary thromboembolic obliteration and progressive pulmonary vascular remodeling. MSCs were retrieved only in high pressure-exposed  lungs recruited via a homing stromal derived factor-1α/CXCR4 pathway. After MSC administration, a marked and long-lasting improvement of all clinical parameters and a significant change of the proteome level were detected. Beside a variation of liver proteome, such as caspase-3, NF-κB,  collagen1A1, and α-SMA, we also identified more than 300 resident and nonresident lung proteins [e.g., myosin light chain 3 (P16409) or mitochondrial ATP synthase subunit alpha (P15999)]. These results suggest that cell therapy restores lung function and the therapeutic effects of MSCs  may be related to protein-based tissue reconstituting effects.
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ferrer
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.forename: Mihael
authors.initials: M
authors.lastname: Vucur
authors.forename: Victor I
authors.initials: VI
authors.lastname: Peinado
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Go
authors.forename: Catharina
authors.initials: C
authors.lastname: Schreiber
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Richthofen
authors.forename: Augustinus
authors.initials: A
authors.lastname: Bader
authors.forename: Johannes
authors.initials: J
authors.lastname: Haag
authors.forename: Kai H
authors.initials: KH
authors.lastname: Darsow
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Bartel
authors.forename: Harald A
authors.initials: HA
authors.lastname: Lange
authors.forename: Dario
authors.initials: D
authors.lastname: Furlani
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchiarini
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000628:therapy*; D008168:Lung / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats
chemical_list: D000199:Actins; D053148:Caspase 3; D016328:NF-kappa B; C498862:Acta2 protein, rat